Methods and apparatus for using polymer-based beads and hydrogels for cardiac applications

Abstract

Biopolymer beads and hydrogels are useful in the remodeling, repair and reconstruction of the heart, as well as in modification of electrical conduction in the heart. Various types of beads are useful, including beads comprising a core of alginate polymers which may or may not be bonded to peptides; beads comprising a core in which peptides are dispersed with alginate polymers, and a chitosan film ionically bonded to available alginate polymers at the surface of the core; beads comprising a core in which peptides and chitosan derivates are dispersed with alginate polymers and form alginate-peptide complexes to which the chitosan derivatives are bonded; and beads comprising a core of chitosan polymers which may or may not be bonded to peptides. The heart may also be treated with a hydrogel agent comprising alginate polymers and peptides covalently bonded to the alginate polymers.

1 . A kit for treating a heart in a diseased condition comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart that relates to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises a plurality of beads; and    wherein each of the beads comprises a core comprising a plurality of alginate polymers.    
     
     
         2 - 11 . (canceled)  
     
     
         12 . A kit for treating a heart in a diseased condition comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart that relates to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises a plurality of beads; and    wherein each of the beads comprises a core comprising a plurality of chitosan polymers.    
     
     
         13 - 14 . (canceled)  
     
     
         15 . A kit for treating cardiac infarction in a heart, comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to interstitial spaces of a infarcted myocardial region of the heart, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the infarcted myocardial region;  
   wherein the bead-containing agent comprises a plurality of beads having a myocardium-adherent property for lodging within the interstitial spaces to provide structural support to the infarcted myocardial region.    
     
     
         16 - 19 . (canceled)  
     
     
         20 . A kit for treating cardiac arrhythmia in a heart, comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart having electrical activity relating to the cardiac arrhythmia, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises a plurality of beads having a conduction-modifying property for modifying the electrical activity in the myocardial region.    
     
     
         21 - 24 . (canceled)  
     
     
         25 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises a plurality of beads, each encapsulating biological material selected from the group consisting of a cell, a gene, a peptide, a polypeptide, a protein, a neo-tissue, and any combination of one or more of the foregoing.    
     
     
         26 - 29 . (canceled)  
     
     
         30 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises a plurality of beads, each encapsulating biological material selected from the group consisting of a cell, a gene, a peptide, a polypeptide, a protein, a neo-tissue, and any combination of one or more of the foregoing; and    wherein each of the beads has a myocardium-adherent property for lodging within interstitial spaces of the myocardial region to provide structural support thereto.    
     
     
         31 - 35 . (canceled)  
     
     
         36 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a multiple-component agent; and    an agent delivery system for delivering a therapeutically effective amount of the multiple-component agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the multiple-component agent into or in proximity to the myocardial region;  
   wherein the multiple-component agent comprises: 
 a first component;  
 a second component for contributing to the therapeutic effect in conjunction with the first component; and  
 a plurality of beads dispersed in at least one of the first and second components.  
   
     
     
         37 - 46 . (canceled)  
     
     
         47 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises a cell-recruiting material.    
     
     
         48 - 49 . (canceled)  
     
     
         50 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises an angiogenic-initiating material.    
     
     
         51 - 52 . (canceled)  
     
     
         53 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a bead-containing agent; and    an agent delivery system for delivering a therapeutically effective amount of the bead-containing agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the bead-containing agent into or in proximity to the myocardial region;  
   wherein the bead-containing agent comprises one or more materials having cell-recruiting and angiogenic-initiating properties.    
     
     
         54 - 55 . (canceled)  
     
     
         56 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a multiple-component agent; and    an agent delivery system for delivering a therapeutically effective amount of the multiple-component agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the multiple-component agent into or in proximity to the myocardial region;  
   wherein the multiple-component agent comprises: 
 a first component comprising a sodium alginate fully solublized in an aqueous solution; and  
 a second component comprising divalent cations dispersed in solution;  
 and wherein the first component and the second component interact to contribute to a therapeutic effect.  
   
     
     
         57 - 60 . (canceled)  
     
     
         61 . A kit for treating a heart in a diseased condition, comprising: 
 a source of a hydrogel agent; and    an agent delivery system for delivering a therapeutically effective amount of the hydrogel agent from the source to a myocardial region of the heart relating to the diseased condition, the agent delivery system comprising: 
 a proximal portion for coupling to the source; and  
 a distal portion for introducing the hydrogel agent into or in proximity to the myocardial region;  
   wherein the hydrogel agent comprises alginate polymers and peptides adapted for covalent bonding to the alginate polymers.    
     
     
         62 - 64 . (canceled)  
     
     
         65 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and applying a therapeutically effective amount of a bead-containing agent at least in proximity to the myocardial region;    wherein the bead-containing agent comprises a plurality of beads; and wherein each of the beads comprises a core comprising a plurality of alginate polymers.    
     
     
         66 - 78 . (canceled)  
     
     
         79 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a bead-containing agent at least in proximity to the myocardial region;    wherein the bead-containing agent comprises a plurality of beads; and    wherein each of the beads comprises a core comprising a plurality of chitosan polymers.    
     
     
         80 - 84 . (canceled)  
     
     
         85 . A method for treating a cardiac infarction, comprising: 
 identifying an infarcted myocardial region of the heart; and    applying a therapeutically effective amount of a bead-containing agent into interstitial spaces of the infarcted myocardial region;    wherein the bead-containing agent comprises a plurality of beads having a myocardium-adherent property for lodging within the interstitial spaces to provide structural support to the infarcted myocardial region.    
     
     
         86 - 88 . (canceled)  
     
     
         89 . A method for treating a cardiac arrhythmia, comprising: 
 identifying a myocardial region of the heart relating to electrical activity of the heart; and    applying a therapeutically effective amount of a bead-containing agent into the identified myocardial region;    wherein the bead-containing agent comprises a plurality of beads having a conduction-modifying property for modifying the electrical activity of the heart in the identified myocardial region.    
     
     
         90 - 92 . (canceled)  
     
     
         93 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a bead-containing agent at least in proximity to the myocardial region;    wherein the bead-containing agent comprises a plurality of beads, each encapsulating biological material selected from the group consisting of a cell, a gene, a peptide, a polypeptide, a protein, a neo-tissue, and any combination of one or more of the foregoing.    
     
     
         94 - 96 . (canceled)  
     
     
         97 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a bead-containing agent at least in proximity to the myocardial region, the bead-containing agent comprising a plurality of beads;    wherein each of the beads has a myocardium-adherent property for lodging within the interstitial spaces to provide structural support to the infarcted myocardial region; and    wherein each of the beads encapsulates biological material selected from the group consisting of a cell, a gene, a peptide, a polypeptide, a protein, a neo-tissue, and any combination of one or more of the foregoing.    
     
     
         98 - 101 . (canceled)  
     
     
         102 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a multiple-component agent at least in proximity to the myocardial region;    wherein the multiple-component agent comprises: 
 a first component;  
 a second component for contributing to the therapeutic effect in conjunction with the first component; and  
 a plurality of beads dispersed in at least one of the first and second components.  
   
     
     
         103 - 111 . (canceled)  
     
     
         112 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a bead-containing agent at least in proximity to the myocardial region;    wherein the bead-containing agent comprises a cell-recruiting material.    
     
     
         113 . (canceled)  
     
     
         114 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a bead-containing agent at least in proximity to the myocardial region;    wherein the bead-containing agent comprises an angiogenic-initiating material.    
     
     
         115 . (canceled)  
     
     
         116 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a bead-containing agent at least in proximity to the myocardial region;    wherein the bead-containing agent comprises one or more materials having cell-recruiting and angiogenic-initiating properties.    
     
     
         117 . (canceled)  
     
     
         118 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a multiple-component agent at least in proximity to the myocardial region;    wherein the multiple-component agent comprises:    a first component comprising a sodium alginate fully solublized in an aqueous solution; and    a second component comprising divalent cations dispersed in solution;    and wherein the first component and the second component interact to contribute to a therapeutic effect.    
     
     
         119 - 121 . (canceled)  
     
     
         122 . A system for treating a heart condition, comprising: 
 a source comprising a bead-containing agent; and    an applicator for applying a therapeutically effective amount of the bead-containing agent from the container at least in proximity to an identified myocardial region of the heart relating to the heart condition;    wherein the bead-containing agent comprises a plurality of beads, each having a mean diameter of from about 30 μm to about 500 μm and comprising a core comprising a plurality of alginate polymers.    
     
     
         123 - 127 . (canceled)  
     
     
         128 . A method for treating a heart condition, comprising: 
 identifying a myocardial region of the heart relating to the heart condition; and    applying a therapeutically effective amount of a hydrogel agent at least in proximity to the myocardial region;    wherein the hydrogel agent comprises alginate polymers and peptides covalently bonded to the alginate polymers.    
     
     
         129 - 130 . (canceled)